Crohn's disease, ulcerative colitis, and indeterminate colitis are collectively termed inflammatory bowel disease (IBD). Corticosteroids remain the predominant therapy for acute exacerbation of IBD since they provide immediate beneficial effects. However, many patients require short or long-term corticosteroid therapy, which can result in substantial side effects. The immunomodulatory agents, azathioprine and 6-mercaptopurine, have been used for over 20 years to decrease long term steroid exposure. The use of azathioprine in patients with inflammatory bowel disease has been well documented in the adult literature. It has been demonstrated that 67% of adult patients could significantly decrease or terminate their steroid therapy 3-6 months after the introduction of oral immunomodulators. Studies have also shown the safety of these immunomodulators for treating inflammatory bowel disease in both adults and in children. Immunomodulators are now used to significantly decrease the dose of steroids or to eliminate their use altogether. They have been proven effective to induce remission, to maintain remission, and to close fistulae. They may also have a role in preventing post-operative recurrences. Severe side effects occur in a small percentage of patients receiving azathioprine/6-mercaptopurine therapy. These patients were found to have a deficiency in the enzyme thiopurine methyltransferase (TPMT), which controls the conversion of 6-mercaptopurine to its 6-methylmercaptopurine metabolite. Screening for such individuals prior to initiating immunomodulators would be warranted and the patients deficient in this enzyme can be excluded. The immunomodulator agents, azathioprine /6-mercaptopurine, in IBD patients, at lower than expected dosages than those studied for chemotherapy/oncology, have substantial side effects which include bone marrow suppression in 5-25%, infections in 7.4%, hepatitis in 0.3%-5%, pancreatitis in 3.3%, allergic drug reaction in 2%, and rarely transient nausea, rash, fever, alopecia, steatorrhea, or a teratogenic effect on the fetus. There have been isolated case-reports of non-Hodgkin's lymphoma and acute myeloid leukemia in IBD patients treated with immunosuppressive drugs.